Cumulative exposure to impaired fasting glucose and gastrointestinal cancer risk: A nationwide cohort study.

BACKGROUND: Impaired fasting glucose (IFG) is associated with the risk of various cancers, but the cumulative effect of IFG on gastrointestinal cancer risk remains unclear. This study evaluated the association between the cumulative exposure to IFG and gastrointestinal cancer risk. METHODS: The authors extracted data from the Korean National Health Insurance Service and health examination data sets. Among individuals ≥40 years old who were free of diabetes or cancer, 1,430,054 who underwent national health examinations over 4 consecutive years from 2009 to 2012 were selected and followed up until gastrointestinal cancer diagnosis, death, or December 31, 2019. The IFG exposure score (range, 0-4) was based on the number of IFG diagnoses over 4 years. RESULTS: The median follow-up duration was 6.4 years. Consistent normoglycemia for 4 years was found in 44.3% of the population, whereas 5.0% had persistent IFG and 50.7% had intermittent IFG. Compared to the group with an IFG exposure score of 0, groups with IFG exposure scores of 1, 2, 3, and 4 had a 5%, 8%, 9%, and 12% increased risk of gastrointestinal cancer, respectively (score 1: adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 1.01-1.08; score 2: aHR, 1.08; 95% CI, 1.04-1.12; score 3: aHR, 1.09; 95% CI, 1.05-1.14; score 4: aHR, 1.12; 95% CI, 1.06-1.19). Persistent IFG exposure was also associated with higher risks of individual cancer types (colorectum, stomach, pancreas, biliary tract, and esophagus). CONCLUSIONS: Cumulative exposure to IFG is associated with an increased risk of developing gastrointestinal cancer, in a dose-dependent manner. PLAIN LANGUAGE SUMMARY: Hyperglycemia, including both diabetes and prediabetes, has been associated with an increased risk of various cancers. However, the cumulative effect of impaired fasting glucose on the risk of developing gastrointestinal cancer remains unclear. A frequent diagnosis of impaired fasting glucose was dose-dependently associated with a higher risk of developing overall gastrointestinal cancer. Furthermore, risks of individual cancer types increased with persistent impaired fasting glucose. Early detection of hyperglycemia and strict glycemic control can lower the risk of gastrointestinal cancer by reducing hyperglycemic burden. Additionally, for some individuals, lifestyle changes such as managing metabolic syndrome or abstaining from alcohol may also be helpful.

IDH2 regulates macrophage polarization and tumorigenesis by modulating mitochondrial metabolism in macrophages.

BACKGROUND: Targeting the tumor microenvironment represents an emerging therapeutic strategy for cancer. Macrophages are an essential part of the tumor microenvironment. Macrophage polarization is modulated by mitochondrial metabolism, including oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, and reactive oxygen species content. Isocitrate dehydrogenase 2 (IDH2), an enzyme involved in the TCA cycle, reportedly promotes cancer progression. However, the mechanisms through which IDH2 influences macrophage polarization and modulates tumor growth remain unknown. METHODS: In this study, IDH2-deficient knockout (KO) mice and primary cultured bone marrow-derived macrophages (BMDMs) were used. Both in vivo subcutaneous tumor experiments and in vitro co-culture experiments were performed, and samples were collected for analysis. Western blotting, RNA quantitative analysis, immunohistochemistry, and flow cytometry were employed to confirm changes in mitochondrial function and the resulting polarization of macrophages exposed to the tumor microenvironment. To analyze the effect on tumor cells, subcutaneous tumor size was measured, and growth and metastasis markers were identified. RESULTS: IDH2-deficient macrophages co-cultured with cancer cells were found to possess increased mitochondrial dysfunction and fission than wild-type BMDM. Additionally, the levels of M2-associated markers decreased, whereas M1-associated factor levels increased in IDH2-deficient macrophages. IDH2-deficient macrophages were predominantly M1. Tumor sizes in the IDH2-deficient mouse group were significantly smaller than in the wild-type mouse group. IDH2 deficiency in macrophages was associated with inhibited tumor growth and epithelial-mesenchymal transition. CONCLUSIONS: Our findings suggest that IDH2 deficiency inhibits M2 macrophage polarization and suppresses tumorigenesis. This study underlines the potential contribution of IDH2 expression in macrophages and tumor microenvironment remodeling, which could be useful in clinical cancer research.

Clinical outcomes of conjunctivochalasis treatment with a new ophthalmic radiofrequency device.

PURPOSE: To investigate the safety and efficacy of a new micro-controlled radiofrequency device for treatment of conjunctivochalasis (Cch). METHODS: Data of 127 patients (230 eyes) who underwent ophthalmic radiofrequency treatment for Cch from January 2020 to June 2023 were analyzed retrospectively. Cch coagulation was performed with a radiofrequency electrode tip (OcuRF®, Ilooda, Korea) and a high-frequency radio-wave electric unit (0.6 ~ 0.8 watts, 2 MHz, Acutron™, Ilooda, Korea). Pre- and postoperative Cch grading, slit-lamp photography, tear film break-up time (TBUT), and bulbar conjunctival hyperemia using Keratograph 5 M (Oculus, Wetzlar, Germany) were evaluated. Cch grade 0 or 1 after surgery was regarded as 'success'. Complications, recurrence, and additional treatment rates were analyzed. RESULTS: In 227 (98.7%) eyes, the radiofrequency treatment led to marked improvement of Cch, with 224 (97.4%) eyes achieving grade 0 or 1 at 2 months postoperatively. Eight eyes (3.5%) received additional treatment. TBUT improved from 3.17 ± 0.82 s to 5.28 ± 1.10 s after surgery (P < 0.001). The total bulbar conjunctival hyperemia value showed an improvement from 1.7 ± 0.6 to 1.4 ± 0.6 postoperatively (P < 0.05). No serious complications were observed. CONCLUSION: The novel ophthalmic radiofrequency device led to a marked improvement of Cch with no serious adverse events during the entire follow-up period. Our results suggest that the radiofrequency device presents a safe and efficacious treatment option for Cch.

Therapeutic Phage Candidates for Targeting Prevalent Sequence Types of Carbapenem-Resistant Escherichia coli.

Carbapenem-resistant Escherichia coli (CREC) is a global threat to public health; therefore, alternative treatment options are urgently needed. Bacteriophages have emerged as promising candidates for combating CREC infections. This study aimed to investigate the genetic basis of phage sensitivity in CREC by evaluating carbapenem resistance among multidrug-resistant (MDR) E. coli isolated in Daegu, South Korea and analyzing their sequence types (STs) with phage susceptibility spectra. Among the 60 MDR E. coli isolates, 80.4% were identified as CREC, with 77.0% demonstrating resistance to imipenem and 66.6% to meropenem. Moreover, 70 lytic E. coli bacteriophages were isolated from hospital sewage water and evaluated against those 60 E. coli isolates. The phages exhibited lytic activity of 33%-60%, with average titers ranging from 5.6 × 1012 to 2.4 × 1013 PFU/mL (Plaque-Forming Unit). Furthermore, multilocus sequence typing (MLST) analysis of the bacterial isolates revealed 14 distinct STs, mostly belonging to ST131, ST410, and ST648. Notably, the phage susceptibility spectra of ST73, ST13003, ST648, ST2311, ST167, ST405, ST607, ST7962, and ST131 were significantly different. Thus, the isolated phages can effectively lyse CREC isolates, particularly those with clinically dominant STs. Conversely, ST410 exhibited a 14.2%-87.14% susceptibility spectrum, whereas ST1139, ST1487, ST10, and ST206 did not lyse, suggesting the presence of more resistant STs. Future studies are warranted to identify the reasons behind this resistance and address it. Ultimately, this study will aid in developing focused treatments to address these pressing global health issues.

Lower risk of depression after smoking cessation and alcohol abstinence in patients with gastric cancer who underwent gastrectomy: A population-based, nationwide cohort study.

BACKGROUND: Although depression is associated with poor treatment outcomes in patients with cancer, little is known about whether lifestyle modifications could help prevent depression. The authors aimed to identify the effect of lifestyle modifications, including smoking cessation, alcohol abstinence, and starting regular physical activity, on new-onset depression in patients with gastric cancer who underwent surgery. METHODS: By using the Korean National Health Insurance Service database, patients with gastric cancer who underwent surgery between 2010 and 2017 were identified. Self-reported lifestyle behaviors within 2 years before and after surgery were analyzed using the health examination database. Patients were classified according to changes in lifestyle behaviors, and their risk of new-onset depression was compared. RESULTS: Among 18,902 patients, 2302 (12.19%) developed depression (26.00 per 1000 person-years). Smoking cessation (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.66-0.91) and alcohol abstinence (HR, 0.79; 95% CI, 0.69-0.90) were associated with reduced risk of depression development compared with persistent smoking and persistent drinking, respectively. Starting regular physical activity was not associated with risk of depression. When lifestyle behaviors after gastrectomy were scored from 0 to 3 points (1 point each for not smoking, not drinking, and being physically active), the risk of depression tended to decrease as lifestyle scores increased from 0 points (reference) to 1 point (HR, 0.69; 95% CI, 0.55-0.83), 2 points (HR, 0.60; 95% CI, 0.50-0.76), and 3 points (HR, 0.55; 95% CI, 0.45-0.68). CONCLUSIONS: Smoking cessation and alcohol abstinence are associated with reduced risk of developing depression in patients with gastric cancer who undergo surgery.

Gastric mucosal swab as an alternative to biopsy for Helicobacter pylori detection.

BACKGROUND AND AIMS: Gastric mucosal swab may be a more sensitive sampling method than a biopsy since Helicobacter pylori (H. pylori) resides within the mucus layer. We compared the diagnostic performance of the rapid urease test (RUT) and bacterial load of H. pylori between swabs and tissue biopsy. METHODS: Overall, 276 RUTs (138 swab-RUTs (S-RUT) and 138 tissue-RUTs (T-RUT)) were performed. To diagnose H. pylori infection, RUT, H. pylori PCR, and 16S ribosomal RNA gene sequencing of tissue and swab were used, and its infection was defined as at least two positives of the six test results. The diagnostic performances of RUTs and the H. pylori bacterial load using qPCR were compared between swab and biopsy. RESULTS: The positivity rates of S-RUT and T-RUT were 35.5% (49/138) and 25.4% (35/138), respectively. The sensitivity, specificity, and accuracy of S-RUT were 98.0%, 100.0%, and 99.2%, while those of T-RUT were 70.0%, 100%, and 89.1%, respectively. The sensitivity and accuracy were significantly higher for S-RUT than for T-RUT (p < 0.05). In the patients with atrophic gastritis and intestinal metaplasia, S-RUT showed significantly higher sensitivity than T-RUT. qPCR showed that the swab contained a significantly higher H. pylori bacterial load than tissue biopsy (22.92-fold and 31.61-fold in the antrum and body (p < 0.05), respectively). CONCLUSIONS: Gastric mucosal swabs showed higher RUT accuracy and H. pylori bacterial load than a tissue biopsy. This may be an alternative to a biopsy when diagnosing H. pylori infection during endoscopy is necessary. (ClinicalTrials.gov, NCT05349578).

Metachronous gastric neoplasm beyond 5 years after endoscopic resection for early gastric cancer.

BACKGROUND AND AIMS: The natural course of early gastric cancer (EGC) following endoscopic submucosal dissection (ESD) remains unclear. This study aimed to clarify the long-term clinical outcomes and risk factors of metachronous gastric neoplasm (MGN) 5 years after ESD for EGC. METHODS: We performed a retrospective analysis of patients who underwent ESD for EGC from July 2005 to October 2015 in Seoul National University Hospital. Long-term clinical outcomes and risk factors of MGN after 5 years post-ESD were evaluated. RESULTS: Among the 2059 patients who underwent ESD for EGC, 1102 were followed up for > 5 years. MGN developed in 132 patients 5 years after ESD. During the median follow-up period of 85 months, the cumulative incidences of MGN and metachronous gastric cancer were 11.7, 16.9, and 27.0 and 7.6, 10.8, and 18.7% after 5, 7, and 10 years, respectively. In multivariable analysis, male sex (odds ratio 1.770; P = 0.042), severe intestinal metaplasia (odds ratio 1.255; P = 0.000), tumor-positive lateral margin (odds ratio 2.711; P = 0.008), < 5 mm lateral safety margin (odds ratio 1.568; P = 0.050), and synchronous adenoma (odds ratio 2.612; P = 0.001) were positive predictive factors, and successful eradication of Helicobacter pylori (odds ratio 0.514; P = 0.024) was a negative predictive factor for MGN after 5 years post-ESD. CONCLUSION: The cumulative MGN incidence was high even 5 years post-ESD for EGC. Meticulous long-term endoscopic follow-up is mandatory, especially in male patients with underlying intestinal metaplasia, tumor-positive lateral margins, lateral safety margins of < 5 mm, and synchronous adenomas.

Histamine-2 Receptor Antagonists and Proton Pump Inhibitors Are Associated With Reduced Risk of SARS-CoV-2 Infection Without Comorbidities Including Diabetes, Hypertension, and Dyslipidemia: A Propensity Score-Matched Nationwide Cohort Study.

BACKGROUND: This study aimed to identify the effect of histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) use on the positivity rate and clinical outcomes of coronavirus disease 2019 (COVID-19). METHODS: We performed a nationwide cohort study with propensity score matching using medical claims data and general health examination results from the Korean National Health Insurance Service. Individuals aged ≥ 20 years who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 January and 4 June 2020 were included. Patients who were prescribed H2RA or PPI within 1 year of the test date were defined as H2RA and PPI users, respectively. The primary outcome was SARS-CoV-2 test positivity, and the secondary outcome was the instance of severe clinical outcomes of COVID-19, including death, intensive care unit admission, and mechanical ventilation administration. RESULTS: Among 59,094 patients tested for SARS-CoV-2, 21,711 were H2RA users, 12,426 were PPI users, and 24,957 were non-users. After propensity score matching, risk of SARS-CoV-2 infection was significantly lower in H2RA users (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.74-0.98) and PPI users (OR, 0.62; 95% CI, 0.52-0.74) compared to non-users. In patients with comorbidities including diabetes, dyslipidemia, and hypertension, the effect of H2RA and PPI against SARS-CoV-2 infection was not significant, whereas the protective effect was maintained in patients without such comorbidities. Risk of severe clinical outcomes in COVID-19 patients showed no difference between users and non-users after propensity score matching either in H2RA users (OR, 0.89; 95% CI, 0.52-1.54) or PPI users (OR, 1.22; 95% CI, 0.60-2.51). CONCLUSION: H2RA and PPI use is associated with a decreased risk for SARS-CoV-2 infection but does not affect clinical outcome. Comorbidities including diabetes, hypertension, and dyslipidemia seem to offset the protective effect of H2RA and PPI.

Protective Factors Against Aggression and Antisocial Attitudes Among Probation Youth with Childhood Adversity Histories.

Childhood adversity is linked to adolescent aggression and antisocial attitudes, which are common predictors of delinquency and violence. Early interruption of these negative trajectories is important for preventing serious criminality. Efforts to bolster protective factors such as social-emotional skills and positive relationships may attenuate this link, but research is needed to clarify salient factors for court-involved youth. Using risk assessment data for a diverse sample of youth on probation (N = 5378), this study investigated the role of adverse childhood experiences in increasing aggression and antisocial attitudes and the degree to which protective factors (self-regulation, future orientation, positive parenting, prosocial connections) mitigated those relationships. Multivariate models controlling for antisocial peers demonstrated that childhood maltreatment was the most salient form of adversity for increasing both aggression and antisocial attitudes. All protective factors were associated with reduced aggression and antisocial attitudes and, in moderation models, muted the impact of childhood adversity on both outcomes. These findings highlight the need for practice efforts geared toward bolstering protective factors for youth on probation, especially among those with child maltreatment histories.

Universal School-Based Social and Emotional Learning (SEL) for Diverse Student Subgroups: Implications for Enhancing Equity Through SEL.

School-based, universal social and emotional learning (SEL) has been widely practiced and promoted as a promising approach to prevent youth mental, emotional, and behavioral problems. Although prior research has accumulated robust evidence of the average effects of universal SEL, it remains unclear whether it works similarly or differentially across diverse sociocultural subgroups of students. Investigating subgroup effects has implications for understanding the impact of universal SEL on possible subgroup disparities in student social-emotional competence (SEC). This study examined whether the effects of a universal SEL program on student SEC development differed across diverse student subgroups classified by gender, race, ethnicity, socioeconomic status, disability status, and English learner status. Data came from student SEC progress monitoring collected during a 1-year quasi-experimental study of a universal SEL program (N = 1592; Grades K-2). The results of multigroup latent growth modeling suggest that (a) the intervention effects were slightly larger for Black students, compared to White or other racial-ethnic subgroups, and (b) the effects were not different across other examined subgroups. This study also found that in the comparison condition, the SEC disparities between Black and White students tended to widen throughout the year, whereas in the intervention condition, Black students showed a similar rate of growth as their White peers. Findings suggest that universal SEL may be similarly beneficial across many diverse student subgroups, while it may yield larger benefits among some racially marginalized subgroups, preventing racial disparities from further widening. Yet the benefits of SEL may not be sufficient to reduce existing subgroup disparities. These findings suggest a need for more studies to examine differential effects of universal preventive programs by diverse subgroups to better inform practices that enhance equity in youth outcomes.

Strategic Directions in Preventive Intervention Research to Advance Health Equity.

As commissioned by the Society for Prevention Research, this paper describes and illustrates strategic approaches for reducing health inequities and advancing health equity when adopting an equity-focused approach for applying prevention science evidence-based theory, methodologies, and practices. We introduce an ecosystemic framework as a guide for analyzing, designing, and planning innovative equity-focused evidence-based preventive interventions designed to attain intended health equity outcomes. To advance this process, we introduce a health equity statement for conducting integrative analyses of ecosystemic framework pathways, by describing the role of social determinants, mechanisms, and interventions as factors directly linked to specific health equity outcomes. As background, we present health equity constructs, theories, and research evidence which can inform the design and development of equity-focused intervention approaches. We also describe multi-level interventions that when coordinated can produce synergistic intervention effects across macro, meso, and micro ecological levels. Under this approach, we encourage prevention and implementation scientists to apply and extend these strategic directions in future research to increase our evidence-based knowledge and theory building. A general goal is to apply prevention science knowledge to design, widely disseminate, and implement culturally grounded interventions that incrementally attain specific HE outcomes and an intended HE goal. We conclude with recommendations for conducting equity-focused prevention science research, interventions, and training.

A public health crisis in the university: Impact of crisis response strategies on universities' transparency and post-crisis relationships during COVID 19 pandemic.

During the COVID 19 pandemic, one of the most critical tasks of the university was to effectively communicate with students, faculty, and staff members. This study aims to explore perceived universities' crisis response messages during the pandemic and examine the effectiveness of each response strategy on public relations outcomes. A survey with 346 university students in the U.S., results showed how defensive and accommodative response strategies differently affected PR outcomes. Accommodative strategies generated higher OPR and greater perceived transparency efforts among students, while several defensive strategies affected students' negative evaluations on post-crisis OPR and perceived transparency of their universities. Such results revealed valuable insights that make significant contributions to theory and practices in university crisis communication and management, especially when dealing with public health crises that are seen as external locus of control.

HIFα Regulates Developmental Myelination Independent of Autocrine Wnt Signaling.

The developing CNS is exposed to physiological hypoxia, under which hypoxia-inducible factor α (HIFα) is stabilized and plays a crucial role in regulating neural development. The cellular and molecular mechanisms of HIFα in developmental myelination remain incompletely understood. A previous concept proposes that HIFα regulates CNS developmental myelination by activating the autocrine Wnt/ß-catenin signaling in oligodendrocyte progenitor cells (OPCs). Here, by analyzing a battery of genetic mice of both sexes, we presented in vivo evidence supporting an alternative understanding of oligodendroglial HIFα-regulated developmental myelination. At the cellular level, we found that HIFα was required for developmental myelination by transiently controlling upstream OPC differentiation but not downstream oligodendrocyte maturation and that HIFα dysregulation in OPCs but not oligodendrocytes disturbed normal developmental myelination. We demonstrated that HIFα played a minor, if any, role in regulating canonical Wnt signaling in the oligodendroglial lineage or in the CNS. At the molecular level, blocking autocrine Wnt signaling did not affect HIFα-regulated OPC differentiation and myelination. We further identified HIFα-Sox9 regulatory axis as an underlying molecular mechanism in HIFα-regulated OPC differentiation. Our findings support a concept shift in our mechanistic understanding of HIFα-regulated CNS myelination from the previous Wnt-dependent view to a Wnt-independent one and unveil a previously unappreciated HIFα-Sox9 pathway in regulating OPC differentiation.SIGNIFICANCE STATEMENT Promoting disturbed developmental myelination is a promising option in treating diffuse white matter injury, previously called periventricular leukomalacia, a major form of brain injury affecting premature infants. In the developing CNS, hypoxia-inducible factor α (HIFα) is a key regulator that adapts neural cells to physiological and pathologic hypoxic cues. The role and mechanism of HIFα in oligodendroglial myelination, which is severely disturbed in preterm infants affected with diffuse white matter injury, is incompletely understood. Our findings presented here represent a concept shift in our mechanistic understanding of HIFα-regulated developmental myelination and suggest the potential of intervening with an oligodendroglial HIFα-mediated signaling pathway to mitigate disturbed myelination in premature white matter injury.

Decrease of ceramides with long-chain fatty acids in psoriasis: Possible inhibitory effect of interferon gamma on chain elongation.

Reportedly, decreases in fatty acid (FA) chain length of ceramide (CER) are associated with interferon-γ (IFN-γ), which shows increased expression in psoriasis. However, the underlying mechanism of this association remains unclear. Therefore, in this study, we aimed to clarify this association between FA chain length of CER, IFN-γ, and the major transcriptional factors involving psoriasis. CER profiling according to FA chain length and class was performed in murine epidermis (n = 10 BALB/c mice topically treated with imiquimod, n = 10 controls) and human stratum corneum (SC) (n = 12 psoriasis, n = 11 controls). The expression of lipid synthetic enzymes, including elongases (ELOVLs), in murine epidermis was also measured using RT-PCR. Furthermore, the association of IFN-γ with various enzymes and transcription factors involved in the generation of long-chain CERs was also investigated using in vitro keratinocyte. A significant decrease in the percentage of long-chain CERs was observed in psoriasis-like murine epidermis and human psoriatic SC. Additionally, the expression levels of ELOVL1, ELOVL4, and ceramide synthase3 (CerS3) were significantly decreased in psoriasis-like murine epidermis and IFN-γ-treated keratinocyte. There was also a significant decrease in the expression of transcriptional factors, including peroxisome proliferator-activated receptor (PPAR), in IFN-γ treated keratinocyte. Thus, it could be suggested that IFN-γ may regulate ELOVL and CerS levels by down-regulating the transcriptional factors. Additionally, given the possible involvement of PPARs or liver X receptor agonist in the CER elongation process, they may serve as potential therapeutic agents for lengthening the CER FAs in psoriasis.

Gastric subepithelial tumor: long-term natural history and risk factors for progression.

BACKGROUND: Subepithelial tumors are often detected incidentally during upper gastrointestinal endoscopy. However, their natural history and clinical management have yet to be clearly established. The aim of this study was to evaluate the natural history and risk factors for progression of gastric SETs. METHODS: The study retrospectively reviewed the medical records of patients who were diagnosed with gastric SET using upper gastrointestinal endoscopy between January 2005 and December 2017. Tumor progression was defined by a ≥ 25% increase in diameter. RESULTS: Among 3237 patients, 1859 underwent serial upper gastrointestinal endoscopy for more than six months. Endoscopic ultrasonography was further performed in 733 (39.43%) patients. Resection was performed in 73 (3.93%) patients. Tumor progressed in 138 (7.42%) patients over a mean follow-up period of 59.41 months (range, 5-215 months). In progressed tumors, the mean initial size was 15.01 mm (range, 2-50 mm) and the mean size increment was 12.86 mm (range, 3-50 mm). Large initial tumor size (OR: 1.03, 95% CI: 1.01-1.05), surface ulcer or erosion (OR: 2.47, 95% CI: 1.21-5.06), lobulated shape (OR: 3.76, 95% CI: 2.00-7.06), and middle-third location (OR: 1.65, 95% CI: 1.08-2.52) were significant risk factors for tumor progression. Large SETs had higher rates of progression and tended to grow faster than smaller tumors (r = 0.44, p < 0.001). CONCLUSIONS: The majority of gastric SETs did not increase in size during the long-term follow-up. Serial endoscopy may be sufficient as a follow-up tool for small SETs with intact overlying mucosa without lobulated shape.

Identification of gaze pattern and blind spots by upper gastrointestinal endoscopy using an eye-tracking technique.

BACKGROUND: The lesion detection rate of esophagogastroduodenoscopy (EGD) varies depending on the degree of experience of the endoscopist and anatomical blind spots. This study aimed to identify gaze patterns and blind spots by analyzing the endoscopist's gaze during real-time EGD. METHODS: Five endoscopists were enrolled in this study. The endoscopist's eye gaze tracked by an eye tracker was selected from the esophagogastric junction to the second portion of the duodenum without the esophagus during insertion and withdrawal, and then matched with photos. Gaze patterns were visualized as a gaze plot, blind spot detection as a heatmap, observation time (OT), fixation duration (FD), and FD-to-OT ratio. RESULTS: The mean OT and FD were 11.10 ± 11.14 min and 8.37 ± 9.95 min, respectively, and the FD-to-OT ratio was 72.5%. A total of 34.3% of the time was spent observing the antrum. When observing the body of the stomach, it took longer to observe the high body in the retroflexion view and the low-to-mid body in the forward view. CONCLUSIONS: It is necessary to minimize gaze distraction and observe the posterior wall in the retroflexion view. Our results suggest that eye-tracking techniques may be useful for future endoscopic training and education.

TNF-α Secreted from Macrophages Increases the Expression of Prometastatic Integrin αV in Gastric Cancer.

The tumor microenvironment comprising blood vessels, fibroblasts, immune cells, and the extracellular matrix surrounding cancer cells, has recently been targeted for research in cancer therapy. We aimed to investigate the effect of macrophages on the invasive ability of gastric cancer cells, and studied their potential mechanism. In transcriptome analysis, integrin αV was identified as a gene increased in AGS cells cocultured with RAW264.7 cells. AGS cells cocultured with RAW264.7 cells displayed increased adhesion to the extracellular matrix and greater invasiveness compared with AGS cells cultured alone. This increased invasion of AGS cells cocultured with RAW264.7 cells was inhibited by integrin αV knockdown. In addition, the increase in integrin αV expression induced by tumor necrosis factor-α (TNF-α) or by coculture with RAW264.7 cells was inhibited by TNF receptor 1 (TNFR1) knockdown. The increase in integrin αV expression induced by TNF-α was inhibited by both Mitogen-activated protein kinase (MEK) inhibitor and VGLL1 S84 peptide treatment. Finally, transcription of integrin αV was shown to be regulated through the binding of VGLL1 and TEAD4 to the promoter of integrin αV. In conclusion, our study demonstrated that TNFR1-ERK-VGLL1 signaling activated by TNF-α secreted from RAW264.7 cells increased integrin αV expression, thereby increasing the adhesion and invasive ability of gastric cancer cells.

Apigenin Isolated from Carduus crispus Protects against H2O2-Induced Oxidative Damage and Spermatogenic Expression Changes in GC-2spd Sperm Cells.

Testicular oxidative stress is one of the most common factors underlying male infertility. Welted thistle, Carduus crispus Linn., and its bioactive principles are attracting scientific interest in treating male reproductive dysfunctions. Here, the protective effects of apigenin isolated from C. crispus against oxidative damage induced by hydrogen peroxide (H2O2) and dysregulation in spermatogenesis associated parameters in testicular sperm cells was investigated. Cell viabilities, ROS scavenging effects, and spermatogenic associated molecular expressions were measured by MTT, DCF-DA, Western blotting and real-time RT-PCR, respectively. A single peak with 100% purity of apigenin was obtained in HPLC conditions. Apigenin treated alone (2.5, 5, 10 and 20 µM) did not exhibit cytotoxicity, but inhibited the H2O2-induced cellular damage and elevated ROS levels significantly (p < 0.05 at 5, 10 and 20 µM) and dose-dependently. Further, H2O2-induced down-regulation of antioxidant (glutathione S-transferases m5, glutathione peroxidase 4, and peroxiredoxin 3) and spermatogenesis-associated (nectin-2 and phosphorylated-cAMP response element-binding protein) molecular expression in GC-2spd cells were attenuated by apigenin at both protein and mRNA levels (p < 0.05). In conclusion, our study showed that apigenin isolated from C. crispus might be an effective agent that can protect ROS-induced testicular dysfunctions.

1-Iodohexadecane Alleviates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice: Possible Involvements of the Skin Barrier and Mast Cell SNARE Proteins.

Atopic dermatitis (AD) is a chronic inflammatory dermal disease with symptoms that include inflammation, itching, and dry skin. 1-Iodohexadecane is known as a component of Chrysanthemum boreale essential oil that has an inhibitory effect on AD-like lesions. However, its effects on AD-related pathological events have not been investigated. Here, we explored the effects of 1-iodohexadecane on AD lesion-related in vitro and in vivo responses and the mechanism involved using human keratinocytes (HaCaT cells), mast cells (RBL-2H3 cells), and a 2,4-dinitrochlorobenzene (DNCB)-induced mouse model (male BALB/c) of AD. Protein analyses were performed by immunoblotting or immunohistochemistry. In RBL-2H3 cells, 1-iodohexadecane inhibited immunoglobulin E-induced releases of histamine and ß-hexosaminidase and the expression of VAMP8 protein (vesicle-associated membrane proteins 8; a soluble N-ethylmaleimide-sensitive factor attachment protein receptor [SNARE] protein). In HaCaT cells, 1-iodohexadecane enhanced filaggrin and loricrin expressions; in DNCB-treated mice, it improved AD-like skin lesions, reduced epidermal thickness, mast cell infiltration, and increased filaggrin and loricrin expressions (skin barrier proteins). In addition, 1-iodohexadecane reduced the ß-hexosaminidase level in the serum of DNCB-applied mice. These results suggest that 1-iodohexadecane may ameliorate AD lesion severity by disrupting SNARE protein-linked degranulation and/or by enhancing the expressions of skin barrier-related proteins, and that 1-iodohexadecane has therapeutic potential for the treatment of AD.

Adjuvant therapy with imatinib for an incompletely resected multilobular tumour of bone in a dog.

A 5-year-old neutered male Shiba Inu dog presented with a history of oral bleeding, dysphagia, and depression for 3 weeks. The physical examination revealed a firm mass in the right caudal palatal region along the level of PM4-M2. On the computed tomography, the mass was round-to-oval in shape and 22 mm × 30 mm × 15 mm in size. The mass contained multiple bone attenuated materials with a palatal bone lysis of 4 mm × 6 mm. A complete resection of the mass was proposed; however, the owner declined due to the risk of complications associated with the radical surgery. Therefore, a palliative resection and biopsy of the mass were performed. On the histological examination, the mass was diagnosed as grade 2 multilobular tumour of bone (MTB). Since the mass was incompletely resected, adjuvant therapy was pursued along with targeted therapy using a tyrosine kinase inhibitor. The tumour cells showed overexpression of the receptor of tyrosine kinase for c-KIT, PDGFR-α, PDGFR-ß, and FGFR1 compared to normal tissue cells. Additionally, the cytotoxic effect of imatinib on the MTB cells was confirmed in vitro. Four weeks postoperatively, the administration of imatinib and carprofen was initiated and continued for 259 days. The patient maintained a good functional outcome for 306 days after the initial presentation.